There are many cancers that are difficult to treat and although therapy is available, there appears to exist or to come into existence, a degree of resistance to the therapy. Primary resistance may occur in that cancer is not responsive to treatment from the outset. Secondary or acquired resistance also occurs quite frequently, which means that a therapy to which the patient seems to respond, at a certain time, loses its efficacy.
There are numerous reasons for resistance, for example some cancers are discovered at a late stage and/or a simply not responsive to treatment.
Mechanisms by which cancers avoid the therapeutic effect include but are not limited to:                i) mutations which render the cancer less vulnerable to the treatment (eg mutation of the site of action of the therapy),        ii) active transportation of the drug out of the tumor, for example by p-glycolation,        iii) building up physical defences, for example stroma which inhibit certain immune responses, and        iv) certain cancers develop paths to repair damage caused by some anti-cancer therapies.        
Tumor heterogeneity may also contribute to resistance, where small subpopulations of cells may acquire or stochastically already possess some of the features enabling them to emerge under selective drug pressure. This is a problem that many patients with cancer encounter, and it obviously limits the therapeutic alternatives that are effective and worsens the prognosis.
Thus based on tumor response to the initial therapy, cancer resistance can be broadly classified into two categories, primary and acquired (Meads et al., 2009; Lippert et al., 2011). While primary drug resistance exists prior to any given treatment, acquired resistance occurs after initial therapy. Unfortunately, the majority of patients will likely develop resistance at a certain point of treatment.
Thus there a huge clinical need for improved therapies to address this unmet patient need.
(R)—N4-[3-Chloro-4-(thiazol-2-ylmethoxy)-phenyl]-N6-(4-methyl-4,5,-dihydro-oxazol-2-yl)-quinazoline-4,6-diamine (Varlitinib, ASLAN001 Example 52 disclosed in WO2005/016346), is a small-molecule pan-HER inhibitor. Some of the patients who had previously had several lines of therapy which had failed at some stage were given Varlitinib monotherapy showed a surprising level of efficacy. Thus Varlitinib appears to be efficacious and able to overcome both primary and secondary therapy resistance in cancer.
Thus the present inventors believe that a compound of formula (I), in particular Varlitinib, will be useful in the treatment of refractory and/or resistant cancers.